Changes in growth rate of an experimental solid tumor following increasing doses of cyclophosphamide

Well-defined times for minimum and maximum growth rates of rat hepatoma 3924A were found when cyclophosphamide doses were increased from 50 to 250 mg/kg. Minimum growth rates occurred 8 to 10 days after treatment and maximum growth rates occurred 13 to 16 days after treatment in 5 groups of 10 animals each that received 50, 100, 150, 200, and 250 mg of cyclophosphamide per kg. Tumor growth delay increased from 6 to 18 days when the dose was increased from 50 to 250 mg/kg. The accelerated growth rate of treated tumors on Day 14 after cyclophosphamide (150 mg/kg) was more than twice that of controls on the same day, 0.349 +/- 0.030 (S.E.) (day-1) and 0.156 +/- 0.011 (day-1), respectively. In addition, the accelerated growth rate of treated tumors on Day 14 was greater than that of controls at initiation of treatment, 0.298 +/- 0.026 (day-1) on Day 2. Increased DNA synthetic rate precedes increased tumor cell proliferation, which, in turn, increases tumor volume. Thus, biochemical studies demonstrating increased cellular proliferation confirm accelerated tumor growth following treatment.